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Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia

  • Marc Schumer
  • , Marc C. Colombel
  • , Ihor S. Sawczuk
  • , Glenda Gobé
  • , John Connor
  • , Kathleen M. O'Toole
  • , Carl A. Olsson
  • , Gilbert J. Wise
  • , Ralph Buttyan

Research output: Contribution to journalArticlepeer-review

Abstract

A multiparametric analysis to demonstrate that even brief periods of arterial clamping can initiate extensive cell loss in a rat kidney through the process of apoptosis during the 48-hour period after reperfusion was performed. Microscopic examination of rat renal tissues subject to a 5-, 30-, or 45-minute period of complete ischemia shouted the presence of apoptotic bodies both within and occasionally between renal tubules, appearing as early 12 hours after reperfusion, and increasing in numbers at 24 hours. Furthermore, DNA extracted from such reperfused renal tissue demonstrated the appearance of a distinct "ladder" pattern of DNA fragments after electrophoresis in agarose gels, a phenomenon commonly associated with cells undergoing apoptosis and in contrast to the predominant smear pattern obtained after electrophoresis of DNA extracted from necrotic renal tissue. Finally, messenger RNA (mRNA) encoding sulfated glycoprotein-2, a gene product previously identified to apoptotic renal cells, was found to be highly expressed in the 30-minute arterial clamped rat kidney after 24 hours of reperfusion, but vas not detectable in mRNA extracted from renal tissue after 24 hours chronic infarction. This study demonstrates that a combination of morphologic, biochemical, and molecular markers can be used to distinguish predominant modes of cell death in varying forms of tissue injury. Application of these analytical techniques to renal vascular injury has distinguished that brief periods of complete ischemia initiates a form of cell death (apoptosis) during a subsequent reperfusion phase that is drastically different from cellular necrosis induced by prolonged severe ischemia.

Original languageEnglish
Pages (from-to)831-838
Number of pages8
JournalAmerican Journal of Pathology
Volume140
Issue number4
StatePublished - Apr 1992

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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